Topical Steroid Treatment for Eosinophilic Esophagitis

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00275561
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 2
• Duration (Months): 53
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This was a randomized controlled trial of swallowed fluticasone vs. placebo for eosinophilic esophagitis. Eosinophilic esophagitis is an inflammatory condition in which the wall of the esophagus becomes filled with large numbers of eosinophils, a type of white blood cell. Patients who have this condition have difficulty in swallowing (dysphagia) solid food.

Prior to treatment the patients had biopsies of their esophagus and took questionnaires regarding their symptoms. Treatment was given for 6 weeks, after which biopsies were taken from the esophagus to measure any changes in the tissue from before treatment. The primary endpoint was improvement in dysphagia as measured by the validated Mayo Dysphagia Questionaire. Secondary outcomes included partial symptom response, and histologic (tissue) response to treatment.

Condition or Disease	Intervention/Treatment	Phase
Eosinophilic Esophagitis	Drug: Fluticasone; Drug: Placebo	Phase 2

Detailed Description

This was a double-blind randomized placebo controlled trial to evaluate the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults newly diagnosed with eosinophilic esophagitis (EoE). Participants were randomized to receive aerosolized swallowed fluticasone 880 mcg bid or placebo inhaler swallowed bid for 6 weeks.

Four mid esophageal biopsies were obtained from 10 cm above the squamo-columnar junction; then formalin-fixed and stained with hematoxylin and eosin. All esophageal biopsies were read and scored by a single expert gastrointestinal pathologist. The formalin-fixed paraffin-embedded esophageal biopsies were retrieved and underwent standard major basic protein (MBP) immunofluorescence staining. All special stain slides were then read and scored by another pathologist. 24-hour urine was collected for free cortisol by the standard technique. The original endoscopy was performed before the patient was enrolled in the trial by standard clinical technique. The endoscopy post treatment was done in the clinical research unit by the principal investigator.

Patients kept compliance logs that were reviewed at phone interviews at 2 and 4 weeks time and at the end of study evaluation. Ninety percent compliance was required for study inclusion.

At the end of 6 weeks, a 24-hour urine cortisol was done, and patients underwent a repeat endoscopy while still on treatment. Mid-esophageal biopsies were obtained and evaluated for eosinophil density and mast cell degranulation. At this visit the patients returned dysphagia and side effects questionnaires.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Randomized Placebo-controlled Trial of Swallowed Fluticasone in Treatment of Eosinophilic Esophagitis
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluticasone Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks	Drug: Fluticasone; Aerosolized swallowed fluticasone 880 mg twice a day; Other Names: Flonase Veramyst
Placebo Comparator: Placebo Placebo inhaler swallowed bid for 6 weeks	Drug: Placebo; Placebo inhaler swallowed twice a day for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Response to Dysphagia [2 weeks]

   Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of "no" to the question "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)?"

Secondary Outcome Measures

1. Number of Participants With Partial or Complete Response to Dysphagia [2 weeks]

   Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of "no" to the question "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)?" A partial symptom response was defined as an answer of yes to the above question and a decrease in severity of at least 2 levels, or a decrease in frequency of at least 1 level.

2. Number of Participants With Complete Histologic Response [2 weeks]

   A complete histologic response was defined as >90% decrease in mean eosinophil count/high powered field

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 20 eosinophils / hpf on biopsies from mid esophagus (hpf = high-powered field)

• Abnormal dysphagia questionnaire (question 1a "yes", question 1c > "moderate" and question 2 > "less than once a week") on Mayo Dysphagia Questionnaire.

Exclusion Criteria:

• Clinical evidence of infectious process potentially contributing to dysphagia (e.g., candidiasis, cytomegalovirus, herpes)

• Systemic or topical steroid therapy for any reason over the past 3 months

• Previous steroid treatment for Eosinophilic Esophagitis

• Intolerance to steroid therapy in the past

• Other cause of dysphagia identified at endoscopy (e.g., reflux esophagitis, stricture, web, ring, achalasia, esophageal neoplasm)

• Dilatation of esophagus at time of index endoscopy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Jeffrey A. Alexander, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

• McElhiney J, Lohse MR, Arora AS, Peloquin JM, Geno DM, Kuntz MM, Enders FB, Fredericksen M, Abdalla AA, Khan Y, Talley NJ, Diehl NN, Beebe TJ, Harris AM, Farrugia G, Graner DE, Murray JA, Locke GR 3rd, Grothe RM, Crowell MD, Francis DL, Grudell AM, Dabade T, Ramirez A, Alkhatib M, Alexander JA, Kimber J, Prasad G, Zinsmeister AR, Romero Y. The Mayo Dysphagia Questionnaire-30: documentation of reliability and validity of a tool for interventional trials in adults with esophageal disease. Dysphagia. 2010 Sep;25(3):221-30. doi: 10.1007/s00455-009-9246-8. Epub 2009 Oct 24.

• ClinicalTrials.gov Identifier: NCT00275561
• Other Study ID Numbers: 1488-05
• First Posted: Jan 12, 2006
• Last Update Posted: May 8, 2012
• Last Verified: May 1, 2012

• Keywords provided by , ,: Eosinophilic Esophagitis; Fluticasone; Dysphagia
• Additional relevant MeSH terms: Esophagitis; Eosinophilic Esophagitis; Fluticasone

Study Results

Participant Flow

Recruitment Details	Adult patients with a new diagnosis of eosinophilic esophagitis were recruited at the Mayo Clinic Rochester between 10/2005 and 12/2009.

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks	Placebo inhaler swallowed bid for 6 weeks
Period Title: Overall Study
STARTED	21	21
COMPLETED	19	15
NOT COMPLETED	2	6

Baseline Characteristics

Arm/Group Title	Fluticasone	Placebo	Total
Arm/Group Description	Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks	Placebo inhaler swallowed bid for 6 weeks	Total of all reporting groups
Overall Participants	21	21	42
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	37.5	35	37.5
Sex: Female, Male (Count of Participants)
Female	3 14.3%	5 23.8%	8 19%
Male	18 85.7%	16 76.2%	34 81%
Region of Enrollment (participants) [Number]
United States	21 100%	21 100%	42 100%
Food Impaction > 5 minutes (participants) [Number]
Participants with Food Impaction	16 76.2%	17 81%	33 78.6%
Participants without Food Impaction	5 23.8%	4 19%	9 21.4%
Mean Esophageal Eosinophil Count (eosinophils/high powered field) [Mean (Full Range) ]
Mean (Full Range) [eosinophils/high powered field]	40	40	40

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Response to Dysphagia
Description	Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of "no" to the question "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)?"
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Analysis was run per protocol.

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks	Placebo inhaler swallowed bid for 6 weeks
Measure Participants	19	15
Number [participants]	9 42.9%	6 28.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluticasone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Number of Participants With Partial or Complete Response to Dysphagia
Description	Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of "no" to the question "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)?" A partial symptom response was defined as an answer of yes to the above question and a decrease in severity of at least 2 levels, or a decrease in frequency of at least 1 level.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Analysis was run per protocol.

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks	Placebo inhaler swallowed bid for 6 weeks
Measure Participants	19	15
Number [participants]	12 57.1%	7 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluticasone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Number of Participants With Complete Histologic Response
Description	A complete histologic response was defined as >90% decrease in mean eosinophil count/high powered field
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Analysis was run per protocol.

Arm/Group Title	Fluticasone	Placebo
Arm/Group Description	Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks	Placebo inhaler swallowed bid for 6 weeks
Measure Participants	19	15
Number [participants]	13 61.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluticasone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	Safety was assessed with the side effect questionnaire at weeks 2 and 4 completed by a structured phone interview. The side effect questionnaire had questions on sore throat, hoarseness, white spots in the mouth, irritability, leg swelling, sleep disturbance, appetite change, acne, headache, diarrhea, nausea, and other new symptoms.
Arm/Group Title	Fluticasone		Placebo
Arm/Group Description	Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks		Placebo inhaler swallowed bid for 6 weeks
All Cause Mortality
	Fluticasone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluticasone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Fluticasone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/19 (36.8%)		6/15 (40%)
Gastrointestinal disorders
Sore throat	2/19 (10.5%)	2	3/15 (20%)	3
Esophageal candidiasis	5/19 (26.3%)	5	0/15 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hoarseness	0/19 (0%)	0	3/15 (20%)	3

Limitations/Caveats

The relatively small sample size; unexpected high dropout rate in the placebo group; study commenced before the consensus definition of EoE advising exclusion of gastroesophageal reflux disease (GERD) was established.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.